tbuckley/cabot-search huggingface dataset:
BRAF(V600E) mutation together with loss of Trp53 or pTEN drives the origination of hairy cell leukemia from B-lymphocytes
Authors: Jiajun Yap, Jimin Yuan, Wan Hwa Ng, Gao Bin Chen, Yuen Rong M. Sim, Kah Chun Goh, Joey Teo, Trixie Y. H. Lim, Shee Min Goay, Jia Hao Jackie Teo, Zhentang Lao, Paula Lam, Kanaga Sabapathy, Jiancheng Hu
Journal: Molecular Cancer (2023)

Abstract Hairy cell leukemia (HCL) is a B-lymphoma induced by BRAF(V600E) mutation. However, introducing BRAF(V600E) in B-lymphocytes fails to induce hematological malignancy, suggesting that BRAF(V600E) needs concurrent mutations to drive HCL ontogeny. To resolve this issue, here we surveyed human HCL genomic sequencing data. Together with previous reports, we speculated that the tumor suppressor TP53, P27, or PTEN restrict the oncogenicity of BRAF(V600E) in B-lymphocytes, and therefore that their loss-of-function facilitates BRAF(V600E)-driven HCL ontogeny. Using genetically modified mouse models, we demonstrate that indeed BRAF(V600E) KI together with Trp53 KO or pTEN KO in B-lymphocytes induces chronic lymphoma with pathological features of human HCL. To further understand the cellular programs essential for HCL ontogeny, we profiled the gene expression of leukemic cells isolated from BRAF(V600E) KI and Trp53 KO or pTEN KO mice, and found that they had similar but different gene expression signatures that resemble that of M2 or M1 macrophages. In addition, we examined the expression signature of transcription factors/regulators required for germinal center reaction and memory B cell versus plasma cell differentiation in these leukemic cells and found that most transcription factors/regulators essential for these programs were severely inhibited, illustrating why hairy cells are arrested at a transitional stage between activated B cells and memory B cells. Together, our study has uncovered concurrent mutations required for HCL ontogeny, revealed the B cell origin of hairy cells and investigated the molecular basis underlying the unique pathological features of the disease, with important implications for HCL research and treatment.
New liposome-radionuclide-chelate combination for tumor targeting and rapid healthy tissue clearance
Authors: Izumi O. Umeda, Yusuke Koike, Mayumi Ogata, Emi Kaneko, Shusei Hamamichi, Tomoya Uehara, Kunikazu Moribe, Yasushi Arano, Tadayuki Takahashi, Hirofumi Fujii
Journal: Journal of Controlled Release (2023)
Development of constitutively synergistic nanoformulations to enhance chemosensitivity in T-cell leukemia
Authors: James M. Kelvin, Madison L. Chimenti, Dan Y. Zhang, Evelyn K. Williams, Samuel G. Moore, Gabrielle M. Humber, Travon A. Baxter, Lacey A. Birnbaum, Min Qui, Henry Zecca, Aashis Thapa, Juhi Jain, Nathan T. Jui, Xiaodong Wang, Haian Fu, Yuhong Du, Melissa L. Kemp, Wilbur A. Lam, Douglas K. Graham, Deborah DeRyckere, Erik C. Dreaden
Journal: Journal of Controlled Release (2023)
Engineering strategies and optimized delivery of exosomes for theranostic application in nerve tissue
Authors: Qicheng Li, Xiaoyang Fu, Yuhui Kou, Na Han
Journal: Theranostics (2023)

Severe injuries or diseases affecting the peripheral and central nervous systems can result in impaired organ function and permanent paralysis.Conventional interventions, such as drug administration and cell-based therapy, exhibit limited effectiveness due to their inability to preserve post-implantation cell survival and impede the deterioration of adjacent tissues.Exosomes have recently emerged as powerful tools for tissue repair owing to their proteins and nucleic acids, as well as their unique phospholipid properties, which facilitate targeted delivery to recipient cells.Engineering exosomes, obtained by manipulating the parental cells or directly functionalizing exosomes, play critical roles in enhancing regenerative repair, reducing inflammation, and maintaining physiological homeostasis.Furthermore, exosomes have been shown to restore neurological function when used in combination with biomaterials.This paper primarily focuses on the engineering strategies and delivery routes of exosomes related to neural research and emphasizes the theranostic application of optimized exosomes in peripheral nerve, traumatic spinal cord, and brain injuries.Finally, the prospects of exosomes development and their combination with other approaches will be discussed to enhance our knowledge on their theranostic effectiveness in neurological diseases.
Global analysis of HLA-A2 restricted MAGE-A3 tumor antigen epitopes and corresponding TCRs in non-small cell lung cancer
Authors: Bei Zhang, Zhiyao Ren, Jianfu Zhao, Yue Zhu, Boya Huang, Chanchan Xiao, Yan Zhang, Jieping Deng, Lipeng Mao, Lei Tang, Dan Lan, Lijuan Gao, Hongyi Zhang, Guobing Chen, Oscar Junhong Luo
Journal: Theranostics (2023)

Background: Advanced non-small cell lung cancer (NSCLC) is the most common type of lung cancer with poor prognosis.Adoptive cell therapy using engineered T-cell receptors (TCRs) targeting cancer-testis antigens, such as Melanoma-associated antigen 3 (MAGE-A3), is a potential approach for the treatment of NSCLC.However, systematic analysis of T cell immune responses to MAGE-A3 antigen and corresponding antigen-specific TCR is still lacking.Methods: In this study, we comprehensively screened HLA-A2 restricted MAGE-A3 tumor epitopes and characterized the corresponding TCRs using in vitro artificial antigen presentation cells (APC) system, single-cell transcriptome and TCR V(D)J sequencing, and machine-learning.Furthermore, the tumor-reactive TCRs with killing potency was screened and verified.Results: We identified the HLA-A2 restricted T cell epitopes from MAGE-A3 that could effectively induce the activation and cytotoxicity of CD8+ T cells using artificial APC in vitro.A cohort of HLA-A2+ NSCLC donors demonstrated that the number of epitope specific CD8+ T cells increased in NSCLC than healthy controls when measured with tetramer derived from the candidate MAGE-A3 epitopes, especially epitope Mp4 (MAGE-A3: 160-169, LVFGIELMEV).Statistical and machine-learning based analyses demonstrated that the MAGE-A3-Mp4 epitope-specific CD8+ T cell clones were mostly in effector and proliferating state.Importantly, T cells artificially expressing the MAGE-A3-Mp4 specific TCRs exhibited strong MAGE-A3+ tumor cell recognition and killing effect.Cross-reactivity risk analysis of the candidates TCRs showed high binding stability to MAGE-A3-Mp4 epitope and low risk of cross-reaction.Conclusions: This work identified candidate TCRs potentially suitable for TCR-T design targeting HLA-A2 restricted MAGE-A3 tumor antigen.
Protein phosphatase 2A-B55β mediated mitochondrial p-GPX4 dephosphorylation promoted sorafenib-induced ferroptosis in hepatocellular carcinoma via regulating p53 retrograde signaling
Authors: Bo Qian, Lin Che, Ze-Bang Du, Ni-Jun Guo, Xin-Mou Wu, Lei Yang, Zhao-Xuan Zheng, Yun-Lu Gao, Ming-Zhu Wang, Xiao-Xuan Chen, Ling Xu, Zi-Jian Zhou, Yu-Chun Lin, Zhong-Ning Lin
Journal: Theranostics (2023)

Rationale: As a key endogenous negative regulator of ferroptosis, glutathione peroxidase 4 (GPX4) can regulate its antioxidant function through multiple post-translational modification pathways. However, the effects of the phosphorylation/dephosphorylation status of GPX4 on the regulation of inducible ferroptosis in hepatocellular carcinoma (HCC) remain unclear. Methods: To investigate the effects and molecular mechanism of GPX4 phosphorylation/dephosphorylation modification on ferroptosis in HCC cells. Sorafenib (Sora) was used to establish the ferroptosis model in HCC cells in vitro. Using the site-directed mutagenesis method, we generated the mimic GPX4 phosphorylation or dephosphorylation HCC cell lines at specific serine sites of GPX4. The effects of GPX4 phosphorylation/dephosphorylation modification on ferroptosis in HCC cells were examined. The interrelationships among GPX4, p53, and protein phosphatase 2A-B55β subunit (PP2A-B55β) were also explored. To explore the synergistic anti-tumor effects of PP2A activation on Sora-administered HCC, we established PP2A-B55β overexpression xenograft tumors in a nude mice model in vivo. Results: In the Sora-induced ferroptosis model of HCC in vitro, decreased levels of cytoplasmic and mitochondrial GPX4, mitochondrial dysfunction, and enhanced p53 retrograde signaling occurred under Sora treatment. Further, we found that mitochondrial p53 retrograded remarkably into the nucleus and aggravated Sora-induced ferroptosis. The phosphorylation status of GPX4 at the serine 2 site (GPX4Ser2) revealed that mitochondrial p-GPX4Ser2 dephosphorylation was positively associated with ferroptosis, and the mechanism might be related to mitochondrial p53 retrograding into the nucleus. In HCC cells overexpressing PP2A-B55β, it was found that PP2A-B55β directly interacted with mitochondrial GPX4 and promoted Sora-induced ferroptosis in HCC. Further, PP2A-B55β reduced the interaction between mitochondrial GPX4 and p53, leading to mitochondrial p53 retrograding into the nucleus. Moreover, it was confirmed that PP2A-B55β enhanced the ferroptosis-mediated tumor growth inhibition and mitochondrial p53 retrograde signaling in the Sora-treated HCC xenograft tumors. Conclusion: Our data uncovered that the PP2A-B55β/p-GPX4Ser2/p53 axis was a novel regulatory pathway of Sora-induced ferroptosis. Mitochondrial p-GPX4Ser2 dephosphorylation triggered ferroptosis via inducing mitochondrial p53 retrograding into the nucleus, and PP2A-B55β was an upstream signal modulator responsible for mitochondrial p-GPX4Ser2 dephosphorylation. Our findings might serve as a potential theranostic strategy to enhance the efficacy of Sora in HCC treatment through the targeted intervention of p-GPX4 dephosphorylation via PP2A-B55β activation.
Multimodal assessment of non-alcoholic fatty liver disease with transmission-reflection optoacoustic ultrasound
Authors: Berkan Lafci, Anna Hadjihambi, Madita Determann, Christos Konstantinou, Clara Freijo, Joaquin L. Herraiz, Sena Blümel, Luc Pellerin, Neal C. Burton, Xosé Luís Deán-Ben, Daniel Razansky
Journal: Theranostics (2023)

Non-alcoholic fatty liver disease (NAFLD) is an umbrella term referring to a group of conditions associated to fat deposition and damage of liver tissue. Early detection of fat accumulation is essential to avoid progression of NAFLD to serious pathological stages such as liver cirrhosis and hepatocellular carcinoma. Methods: We exploited the unique capabilities of transmission-reflection optoacoustic ultrasound (TROPUS), which combines the advantages of optical and acoustic contrasts, for an early-stage multi-parametric assessment of NAFLD in mice. Results: The multispectral optoacoustic imaging allowed for spectroscopic differentiation of lipid content, as well as the bio-distributions of oxygenated and deoxygenated hemoglobin in liver tissues in vivo. The pulse-echo (reflection) ultrasound (US) imaging further provided a valuable anatomical reference whilst transmission US facilitated the mapping of speed of sound changes in lipid-rich regions, which was consistent with the presence of macrovesicular hepatic steatosis in the NAFLD livers examined with ex vivo histological staining. Conclusion: The proposed multimodal approach facilitates quantification of liver abnormalities at early stages using a variety of optical and acoustic contrasts, laying the ground for translating the TROPUS approach toward diagnosis and monitoring NAFLD in patients.
DNMT1 mediates the disturbed flow-induced endothelial to mesenchymal transition through disrupting β-alanine and carnosine homeostasis
Authors: Jianan Zhao, Chuanrong Zhao, Fangfang Yang, Zhitong Jiang, Juanjuan Zhu, Weijuan Yao, Wei Pang, Jing Zhou
Journal: Theranostics (2023)

Background: Increasing evidence suggests that hemodynamic disturbed flow induces endothelial dysfunction via a complex biological process so-called endothelial to mesenchymal transition (EndoMT). Recently, DNA methyltransferases (DNMTs) was reported as a key molecular mediator to promote EndoMT. Our understanding of how DNMTs, particularly the maintenance DNMTs, DNMT1, coordinate EndoMT is still lacking. Methods: A parallel-plate flow apparatus and perfusion devices were used to apply fluid with endothelial protective pulsatile shear (PS, to mimic the laminar flow) or harmful oscillatory shear (OS, to mimic the disturbed flow) to cultured endothelial cells (ECs). Endothelial lineage tracing mice and conditional EC Dnmt1 knockout mice were subjected to a surgery of carotid partial ligation to generate the flow-accelerated atherogenesis models. Western blotting, quantitative RT-PCR, immunofluorescent staining, methylation-specific PCR, chromatin immunoprecipitation, endothelial functional assays, and assessments for neointimal formation and atherosclerosis were performed. Results: Inhibition of DNMTs with 5-aza-2'-deoxycytidine (5-Aza) suppressed the disturbed flow/OS-induced EndoMT, both in cultured cells and the endothelial lineage tracing mice. 5-Aza also ameliorated the downregulation of aldehyde dehydrogenases (ALDHs) and β-alanine biosynthesis caused by disturbed flow/OS. Knockdown of the ALDH family proteins, ALDH2, ALDH3A1, and ALDH6A1, showed an EndoMT-induction effect as OS. Supplementation of cells with the functional metabolites of β-alanine, carnosine and acetyl-CoA (acetate), reversed EndoMT, likely via inhibiting the phosphorylation of Smad2/3. Endothelial-specific knockout of Dnmt1 protected the vasculature from disturbed flow-induced remodeling and atherosclerosis. Conclusions: Endothelial DNMT1 acts as one of the key epigenetic factors to mediate the hemodynamically regulated EndoMT at least through repressing the expression of ALDH2, ALDH3A1, and ALDH6A1. Supplementation with carnosine and acetate may have a great potential in the prevention and treatment of atherosclerosis.
Use of Medication for Opioid Use Disorder Among Adults With Past-Year Opioid Use Disorder in the US, 2021
Authors: Christopher M. Jones, Beth Han, Grant T. Baldwin, Emily B. Einstein, Wilson M. Compton
Journal: JAMA Network Open (2023)

This cross-sectional study uses data from the 2021 National Survey on Drug Use and Health to estimate the receipt of medication for opioid use disorder among US adults with past-year opioid use disorder.
Author correction to “Immune-awakening Saccharomyces-inspired nanocarrier for oral target delivery to lymph and tumors” [Acta Pharmaceutica Sinica B 12 (2022) 4501–4518]
Authors: Yuling Mao, Xiudan Wang, Caishun Chen, Qinfu Zhao, Yanfeng Liu, Jinghai Zhang, Siling Wang
Journal: Acta Pharmaceutica Sinica B (2023)

[This corrects the article DOI: 10.1016/j.apsb.2022.04.018.].
Prolonging Treatment Window of Photodynamic Therapy with Self‐Amplified H<sub>2</sub>O<sub>2</sub>‐Activated Photodynamic/Chemo Combination Therapeutic Nanomedicines
Authors: Shanchao Diao, Yaxin Liu, Zixin Guo, Zhiwei Xu, Jinlong Shen, Wen Zhou, Chen Xie, Quli Fan
Journal: Advanced Healthcare Materials (2023)

Abstract Photodynamic therapy (PDT) is a promising approach to cancer therapy. However, the relatively short tumor retention time of photosensitizers (PSs) makes it difficult to catch the optimal treatment time and restricts multiple PDT within a single injection. In this study, a tumor‐specific phototheranostic nanomedicine (DPPa NP) is developed for photodynamic/chemo combination therapy with a prolonged PDT treatment window. DPPa NP is prepared via encapsulating a hydrophobic oxidized bovine serum albumin (BSA‐SOH)‐conjugatable PS DPPa with amphiphilic H 2 O 2 ‐activatable chlorambucil (CL) prodrug mPEG‐TK‐CL. The released CL under H 2 O 2 treatment can not only kill tumor cells but also upregulate reactive oxygen species levels within tumor cells, leading to the almost full release of cargoes. The released DPPa may conjugate with overexpressed BSA‐SOH, which results in the recovery of the fluorescence signal and photodynamic effect. More importantly, such conjugation transfers DPPa from a small molecule PS into a macromolecular PS with a long tumor retention time and treatment window of PDT, which enables multiple PDT. This study thus provides an effective strategy to prolong the treatment window of PDT and enables tumor‐specific fluorescence imaging‐guided combination therapy.
Prospective Associations of Different Combinations of Aerobic and Muscle-Strengthening Activity With All-Cause, Cardiovascular, and Cancer Mortality
Authors: Rubén López-Bueno, Matthew Ahmadi, Emmanuel Stamatakis, Lin Yang, Borja del Pozo Cruz
Journal: JAMA Internal Medicine (2023)

Studies examining the associations of different combinations of intensity-specific aerobic and muscle strengthening activity (MSA) with all-cause and cause-specific mortality are scarce; the few available estimates are disparate.
Author correction to “Coordinated regulation of BACH1 and mitochondrial metabolism through tumor targeted self-assembled nanoparticles for effective triple negative breast cancer combination therapy” [Acta Pharmaceutica Sinica B 12 (2022) 3934–3951]
Authors: Xuan Yang, Yalong Wang, Junke Zhao, Hehui Rong, Yujun Chen, Mengting Xiong, Xiaoxing Ye, Shihui Yu, Haiyan Hu
Journal: Acta Pharmaceutica Sinica B (2023)

[This corrects the article DOI: 10.1016/j.apsb.2022.06.009.].
There Is No 1-Size-Fits-All to Blood Pressure Measurement—Cuff Size Matters
Authors: Mathias Lalika, Stephen P. Juraschek, LaPrincess C. Brewer
Journal: JAMA Internal Medicine (2023)

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First-in-Human Transapical Beating-Heart Septal Myectomy in Patients With Hypertrophic Obstructive Cardiomyopathy
Authors: Jing Fang, Yani Liu, Ying Zhu, Rui Li, Rui Wang, Dao Wen Wang, Yunhu Song, Chenhe Li, Yue Chen, Lin Cheng, Kangchao Zheng, Yun Zhao, Shiliang Li, Cai Cheng, Liming Xia, Xiaoping Chen, Song Wan, Xiang Wei
Journal: Journal of the American College of Cardiology (2023)
FOXO1 orchestrates the intestinal homeostasis via neuronal signaling in group 3 innate lymphoid cells
Authors: Fei Shao, Zhen Liu, Qinglin Wei, Dou Yu, Min Zhao, Xusheng Zhang, Xintong Gao, Zusen Fan, Shuo Wang
Journal: The Journal of Experimental Medicine (2023)

The neuro-immune regulation is associated with homeostasis of the intestine. Intestinal group 3 innate lymphoid cells (ILC3s) are tissue-resident lymphocytes whose functions are affected by the intestine niche. However, how a gut neuronal signal coordinates the immune response of ILC3s is largely unknown. Here, we found that cyclic adenosine monophosphate (cAMP) signaling exacerbated the inflammatory response and attenuated the expression level of the transcription factor forkhead box O1 (FOXO1) in ILC3s. Deficiency of FOXO1 drove the hyperactivation of ILC3s and resulted in gut inflammation independently of T cells. Mechanistically, FOXO1 promoted the transcription of neuropeptide receptor VIPR2 and inhibited the transcription of adrenoceptor ADRA2A in ILC3s. FOXO1-related regulation of VIPR2 and ADRA2A signaling balanced the activation of ILC3s under steady condition or during colitis. Moreover, chronic stress elevated cAMP level and downregulated FOXO1 level, exacerbating intestinal inflammation. Our findings reveal that FOXO1 balances the activation of ILC3s via VIP and adrenergic signaling and regulates intestinal homeostasis.
Outdoor Worker Stress Monitoring Electronics with Nanofabric Radiative Cooler‐Based Thermal Management
Authors: Hojoong Kim, Young Jin Yoo, Joo Ho Yun, Se‐Yeon Heo, Young Min Song, Woon‐Hong Yeo
Journal: Advanced Healthcare Materials (2023)

Severe stress endangers outdoor workers who are in an exceedingly hot workplace. Although recent studies quantify stress levels on the human skin, they still rely on rigid, bulky sensor modules, causing data loss from motion artifacts and limited field-deployability for continuous health monitoring. Moreover, no prior work shows a wearable device that can endure heat exposure while showing continuous monitoring of a subject's stress under realistic working environments. Herein, a soft, field-deployable, wearable bioelectronic system is introduced for detecting outdoor workers' stress levels with negligible motion artifacts and controllable thermal management. A nanofabric radiative cooler (NFRC) and miniaturized sensors with a nanomembrane soft electronic platform are integrated to measure stable electrodermal activities and temperature in hot outdoor conditions. The NFRC exhibits outstanding cooling performance in sub-ambient air with high solar reflectivity and high thermal emissivity. The integrated wearable device with all embedded electronic components and the NFRC shows a lower temperature (41.1%) in sub-ambient air than the NFRC-less device while capturing improved operation time (18.2%). In vivo human study of the bioelectronics with agricultural activities demonstrates the device's capability for portable, continuous, real-time health monitoring of outdoor workers with field deployability.
Buprenorphine Out-of-Pocket Costs and Discontinuation in Privately Insured Adults With Opioid Use Disorder
Authors: Ashley A. Leech, Elizabeth McNeer, Andrew W. Roberts, Stacie B. Dusetzina, Pikki Lai, Jake R. Morgan, Stephen W. Patrick
Journal: JAMA Internal Medicine (2023)

This cohort study examined the association between out-of-pocket costs for an initial buprenorphine prescription and its discontinuation among commercially insured US adults with opioid use disorder.